Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi.
Resveratrol is found in the skin of red grapes, red wind, and in other fruits. Resveratrol has also been produced by chemical synthesis or by biotechnological synthesis (metabolic engineered microorganisms) and is sold as a nutritional supplement derived primarily from Japanese knotweed.
In 1997, Jang reported that topical resveratrol applications prevented skin cancer development in mice treated with a carcinogen.
Clinical trials to investigate the effects on colon cancer and melanoma (skin cancer) are currently recruiting patients.
The strongest evidence of anti-cancer action of resveratrol exists for tumors it can come into direct contact with, such as skin and gastrointestinal tract tumors. For other cancers, the evidence is uncertain.
Thus, resveratrol (1 mg/kg orally) reduced the number and size of the esophageal tumors in rats treated with a carcinogen; and in several studies, small doses (0.02-8 mg/kg) of resveratrol, given prophylactically, reduced or prevented the development of intestinal and colon tumors in rats given different carcinogens. Similarly, topical application of resveratrol in mice, both before and after the UVB exposure, inhibited the skin damage and decreased skin cancer incidence. Resveratrol given orally also had no effect on leukemia and lung cancer; however, injected intraperitoneally, 2.5 or 10 mg/kg of resveratrol slowed the growth of metastatic Lewis lung carcinomas in mice.
Presently, resveratrol is sold as an anti-aging, anti-wrinkle skin care product for topical application.

However, resveratrol also: exhibits antioxidant, anti-inflammatory, anti-obesity, anti-cancer, anti-viral, anti-diabetic, neuro-protective and cardio-protective activity; has been found to inhibit UVB-induced erythema, edema, hyperplastic response, leukocyte infiltration, COX-2 activity in hairless mice; possibly activates expression of SIRT1 which mimics effects of severe caloric restriction to prolong longevity; and is possibly responsible for “French Paradox” (High fat diet, low rate of CVD). The compositions described herein should increase the effectiveness of resveratrol in all of these uses.
When using topical resveratrol compounds, patients should be advised to incorporate preventative, healthy practices with respect to exposure to the sun. Damaging rays from the sun can penetrate the clouds and even glass. Therefore, people working by a window or riding in a vehicle also risk exposure to damaging rays. Sunscreens are considered the gold standard for protecting the skin from the harmful effects of UV light (Leyden, 2003), and a broad spectrum (UVB/UVA) sunscreen with key ingredients such as Avobenzone provides the most protection. Sunscreen should be applied daily, even on cloudy days and during the winter months. Patients should protect exposed areas of the skin with an appropriate sunscreen 30 minutes prior to exposure, followed by a second application to ensure adequate coverage. Often, once-a-day sunscreen application is not enough and sunscreen should be reapplied throughout the day. When exposed to the elements, sunscreen application is recommended to be applied every 2 hours and more often if sweating or swimming. When feasible, peak hours of the sun should be avoided (10 am to 4 pm), and patients should seek shade when they can. A sun-protection lip balm is also beneficial. If prolonged sun exposure is expected, such as during a vacation, the use of the topical resveratrol compound should be discontinued one week before the exposure and resumed upon return.
One major drawback to the clinical use of resveratrol compounds, especially topically, isomerization of trans-resvervatrol to cis-resveratrol on exposure to UV radiation. The absorption of ultraviolet light causes the excitation of an electron in the trans-resveratrol from an initially occupied, low energy orbital to a higher energy, previously unoccupied orbital. The energy of the absorbed photon is used to energize an electron and cause it to “jump” to a higher energy orbital. Two excited electronic states derive from the electronic orbital configuration produced by UV light absorption. In one state, the electron spins are paired (antiparallel) and in the other state the electron spins are unpaired (parallel). The state with paired spins has no resultant spin magnetic moment, but the state with unpaired spins possesses a net spin magnetic moment. A state with paired spins remains a single state in the presence of a magnetic field, and is termed a singlet state. A state with unpaired spins interacts with a magnetic field and splits into three quantized states, and is termed a triplet state.
When resveratrol compounds are exposed to light, they also undergo photodegradation via a number of pathways, including undesirable isomerization reactions, photoaddition/substitution reactions, and cycloadditions, all of which destroy the integrity of the resveratrol and its ability to function as intended.
This photoinstability of resveratrol compounds, particularly trans-resveratrol, is highly problematic when developing and using topical resveratrol compounds and resveratrol compound-containing compositions for clinical purposes. To reduce the amount of photodegradation that occurs in topical resveratrol compound-containing products, manufacture of the resveratrol product must occur in the dark or under special lighting conditions, and the packaging of the resveratrol product must be light fast. Even if resveratrol compound-containing products are manufactured in the dark and stored in a light fast package, they quickly degrade upon application to the skin, rendering the resveratrol product ineffective.